The effect of
non-insulin-dependent diabetes mellitus (i.e.,
NIDDM;
type 2 diabetes) on the levels of functional mitochondrial
anion transport proteins has been determined utilizing a chemically-induced neonatal model of
NIDDM. We hypothesized that moderate
insulin deficiency exacerbated by the
insulin resistance, which is characteristic of
NIDDM, would cause changes in mitochondrial
anion transporter function that were similar to those we have previously shown to occur in
insulin-dependent diabetes mellitus (i.e.,
IDDM;
type 1 diabetes) (Arch. Biochem. Biophys. 280: 181-191, 1990). Our experimental approach consisted of the extraction of the
pyruvate, dicarboxylate and
citrate transport proteins from the mitochondrial inner membrane with
Triton X-114 using rat liver mitoplasts (prepared from diabetic and control animals) as the starting material, followed by the functional reconstitution of each transporter in a proteoliposomal system. This strategy permitted the quantification of the functional levels of these three transporters in the absence of the complications that arise when such measurements are carried out with intact mitochondria (or mitoplasts). We found that experimental
NIDDM did not cause significant changes in the extractable and reconstitutable specific (and total) transport activities of the
pyruvate, dicarboxylate, and
citrate transporters. These results are in marked contrast to our previous findings obtained using rats with
IDDM and negated our hypothesis. The present results, in combination with our earlier findings, allow us to conclude that
insulin plays an important role in the regulation of mitochondrial
anion transporter function.(ABSTRACT TRUNCATED AT 250 WORDS)